This invention relates to novel polymer-drug compounds and their use in providing sustained release drug delivery to human and other warm-blooded animals. The polymer-drug compounds provide a mechanism whereby the rate of release and availability of the drug may be regulated so that the quantity of a drug which is released at a particular time or at a particular site is relatively constant and uniform over extended periods of time.
Drugs are conventionally administered orally or via injection, often at a site remote from the target. Over a relatively short period of time, the drug diffuses into the circulation system of the patient and is distributed to the various organs, at least one of which is the intended target for the drug. The action of the drug on organs other than the target may result in undesirable side effects. Finally, the drug is metabolized or otherwise irreversibly removed from the organism by excretion or chemical deactivation.
When drugs are delivered orally or by injection, the level and duration of availability of the drug cannot be controlled independently; only the size and frequency of the dose can be manipulated. Typically, there is an initially high concentration of available drug at the site of injection or in the circulatory system which then decreases gradually as the drug is distributed and consumed within the body of the patient.
In controlled sustained delivery, a formulation of the drug is administered to the patient by injection or implantation. The formulation is a drug reservoir that protects the stored drug from extraneous removal mechanisms and releases the drug to the biological reservoir at a predetermined rate.
Controlled sustained delivery of a drug prevents undesirable peaking of blood levels and makes the drug available at an optimum and uniform concentration over an extended period of time. Only the released drug is subject to removal via metabolism and excretion.
U.S. Pat. Nos. 3,773,919 and 3,755,558 describe physical mixtures of various polylactides and copolymers of glycolide and lactide with some well known drugs in order to achieve a slow release of the drugs when implanted or applied topically to humans. These mixtures are intended to release the drug over an extended period of time as the polymer of the mixture is slowly absorbed in the system. However, there exists the possibility that the drugs may be extracted from the mixture by body fluids before the polymers are absorbed, leaving an unnecessary and nonfunctional mass of polymer within the organism, and making the rate of delivery of the drug unpredictable or at lease unrelated to the polymer absorption rate.